Mangosteen xanthones suppress hepatitis C virus genome replication
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Abstract
Hepatitis C virus (HCV) is a hepatotropic single-stranded RNA virus. HCV infection is causally linked with development of liver cirrhosis and hepatocellular carcinoma. Enhanced production of reactive oxygen species by HCV has been implicated to play an important role in HCV-induced pathogenesis. Mangosteen has been widely used as a traditional medicine as well as a dietary supplement ,thanks to its powerful anti-oxidant effect. In the present study, we demonstrated that the ethanol extract from mangosteen fruit peels (MG-EtOH) is able to block HCV genome replication using HCV genotype 1b Bart79I subgenomic (EC50 5.1 μg/mL) and genotype 2a J6/JFH-1 infectious replicon systems (EC50 3.8 μg/mL). We found that inhibition of HCV replication by MG-EtOH led to subsequent down-regulation of expression of HCV proteins. Interestingly, MG-EtOH exhibited a modest inhibitory effect on in vitro RNA polymerase activity of NS5B. Among a number of xanthones compounds identified within this MG-EtOH, we discovered α-MG (EC50 6.3 μM) and γ-MG (EC50 2.7 μM) as two major single molecules responsible for suppression of HCV replication. This finding will provide a valuable molecular basis to further develop mangosteen as an important dietary supplement to combat HCV-induced liver diseases.
Keywords
Hepatitis C virus Mangosteen xanthones Replication inhibitor Anti-oxidant Alpha-mangostin Gamma-mangostinAbbreviations
- HCV
Hepatitis C virus
- ROS
Reactive oxygen species
- HCC
Hepatocellular carcinoma
- MG-EtOH
Magosteen ethanol extract
Notes
Acknowledgments
We would like to thank Dr. Jong-Won Oh for providing all the reagents and advices necessary for in vitro HCV NS5B RNA polymerase assay. This work was supported by the GRRC program of Gyeonggi province [(GRRC-DONGGUK2012-A01), Study of control of viral diseases], [(GRRC-DONGGUK2012-B02), Development and discovery of new therapeutic target modulators]. This research was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A1011851).
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